Method of preparing delta-9-tetrahydrocannabinol esters

Abstract

The present invention provides an economical and efficient process for converting delta-9-tetrahydrocannabinol to a variety of ester analogs. Delta-9-tetrahydrocannabinol is esterified by reaction with a carboxylic acid, an acid halide or an acid anhydride in the presence of a 4-aminopyridine either alone or in admixture with an organic amine such as a mono-, di-, or tri-alkyl amine.

We claim: 
     
       1. A process for the preparation of a compound of the formula: ##STR4## in which R represents an acyl group, said process comprising reacting delta-9-tetrahydrocannabinol with a carboxylic acid, acid halide or acid anhydride having R as the residue group in the presence of a 4-amino-substituted pyridine. 
     
     
       2. The process of claim 1, where the 4-amino-substituted pyridine is a compound of the formula ##STR5## in which R 1 , and R 2  are each independently H, optionally substituted lower alkyl, optionally substituted aryl or R 1  and R 2  can be taken together to form a carbocyclic or heterocyclic 5-or-6 membered ring. 
     
     
       3. The process of claim 1, further comprising carrying out the esterification with the additional presence of a further organic amine. 
     
     
       4. The process of claim 1, in which R is a group of the formula: ##STR6## in which R' is an alkyl containing a carboxyl or an amino group. 
     
     
       5. The process of claim 1, wherein R is the hemiester of succinic acid. 
     
     
       6. The process of claim 1, wherein R is the hemiester of malonic acid. 
     
     
       7. The process of claim 1, wherein the 4-substituted pyridine is 4-pyrrolidinopyridine. 
     
     
       8. The process of claim 1, wherein the 4-substituted pyridine is a 4-diloweralkylaminopyridine. 
     
     
       9. The process of claim 1, wherein the 4-substituted pyridine is 4-dimethylaminopyridine. 
     
     
       10. The process of claim 3, wherein the organic amine is a mono-, di-, or tri-lower alkyl amine. 
     
     
       11. The process of claim 10, wherein the organic amine is triethylamine. 
     
     
       12. The process of claim 1 wherein R is the acyl residue of succinic acid, the acid anhydride is succinic anhydride and the base is a mixture of 4-dimethylamine pyridine and triethylamine. 
     
     
       13. The process of claim 1, wherein the delta-9-tetrahydrocannabinol is reacted with a carboxylic acid. 
     
     
       14. The process of claim 1, wherein the delta-9-tetrahydrocannabinol is reacted with an acid halide. 
     
     
       15. The process of claim 1, wherein the delta-9-tetrahydrocannabinol is reacted with an acid anhydride. 
     
     
       16. The process of claim 1, wherein R represents an acyl group having an alkyl side chain containing a polar group. 
     
     
       17. The process of claim 4, wherein R' is an alkyl containing between 2 to 10 carbon atoms.